SOX2_HUMAN
ID SOX2_HUMAN Reviewed; 317 AA.
AC P48431; Q14537;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Transcription factor SOX-2;
GN Name=SOX2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=7849401; DOI=10.1007/bf00411460;
RA Stevanovic M., Zuffardi O., Collignon J., Lovell-Badge R., Goodfellow P.;
RT "The cDNA sequence and chromosomal location of the human SOX2 gene.";
RL Mamm. Genome 5:640-642(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RA Sadler L.A., Badzioch M.D., Wagner M., Graves K.A., Swaroop A.,
RA Yang-Feng T.L., Zheng K., Daiger S.P.;
RL Submitted (DEC-1992) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INVOLVEMENT IN MCOPS3.
RX PubMed=12612584; DOI=10.1038/ng1120;
RA Fantes J., Ragge N.K., Lynch S.-A., McGill N.I., Collin J.R.O.,
RA Howard-Peebles P.N., Hayward C., Vivian A.J., Williamson K.,
RA van Heyningen V., FitzPatrick D.R.;
RT "Mutations in SOX2 cause anophthalmia.";
RL Nat. Genet. 33:461-463(2003).
RN [5]
RP BIOTECHNOLOGY, AND FUNCTION.
RX PubMed=18035408; DOI=10.1016/j.cell.2007.11.019;
RA Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K.,
RA Yamanaka S.;
RT "Induction of pluripotent stem cells from adult human fibroblasts by
RT defined factors.";
RL Cell 131:861-872(2007).
RN [6]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 42-LYS-ARG-43; 56-ARG--LYS-58 AND
RP 113-ARG--LYS-115.
RX PubMed=19349578; DOI=10.1083/jcb.200810106;
RA Gontan C., Guettler T., Engelen E., Demmers J., Fornerod M., Grosveld F.G.,
RA Tibboel D., Goerlich D., Poot R.A., Rottier R.J.;
RT "Exportin 4 mediates a novel nuclear import pathway for Sox family
RT transcription factors.";
RL J. Cell Biol. 185:27-34(2009).
RN [7]
RP INTERACTION WITH GLIS1.
RX PubMed=21654807; DOI=10.1038/nature10106;
RA Maekawa M., Yamaguchi K., Nakamura T., Shibukawa R., Kodanaka I.,
RA Ichisaka T., Kawamura Y., Mochizuki H., Goshima N., Yamanaka S.;
RT "Direct reprogramming of somatic cells is promoted by maternal
RT transcription factor Glis1.";
RL Nature 474:225-229(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-251, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [9]
RP VARIANTS MCOPS3 ARG-51; PRO-74 AND SER-79$.
RX PubMed=24033328; DOI=10.1111/cge.12275;
RA Chassaing N., Causse A., Vigouroux A., Delahaye A., Alessandri J.L.,
RA Boespflug-Tanguy O., Boute-Benejean O., Dollfus H., Duban-Bedu B.,
RA Gilbert-Dussardier B., Giuliano F., Gonzales M., Holder-Espinasse M.,
RA Isidor B., Jacquemont M.L., Lacombe D., Martin-Coignard D.,
RA Mathieu-Dramard M., Odent S., Picone O., Pinson L., Quelin C., Sigaudy S.,
RA Toutain A., Thauvin-Robinet C., Kaplan J., Calvas P.;
RT "Molecular findings and clinical data in a cohort of 150 patients with
RT anophthalmia/microphthalmia.";
RL Clin. Genet. 86:326-334(2014).
CC -!- FUNCTION: Transcription factor that forms a trimeric complex with OCT4
CC on DNA and controls the expression of a number of genes involved in
CC embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By
CC similarity). Binds to the proximal enhancer region of NANOG (By
CC similarity). Critical for early embryogenesis and for embryonic stem
CC cell pluripotency (PubMed:18035408). Downstream SRRT target that
CC mediates the promotion of neural stem cell self-renewal (By
CC similarity). Keeps neural cells undifferentiated by counteracting the
CC activity of proneural proteins and suppresses neuronal differentiation
CC (By similarity). May function as a switch in neuronal development (By
CC similarity). {ECO:0000250|UniProtKB:P48430,
CC ECO:0000250|UniProtKB:P48432, ECO:0000269|PubMed:18035408}.
CC -!- SUBUNIT: Interacts with ZSCAN10 (By similarity). Interacts with SOX3
CC and FGFR1 (By similarity). Interacts with GLIS1 (PubMed:21654807).
CC Interacts with POU5F1; binds synergistically with POU5F1 to DNA (By
CC similarity). {ECO:0000250|UniProtKB:P48432,
CC ECO:0000269|PubMed:21654807}.
CC -!- INTERACTION:
CC P48431; O95983: MBD3; NbExp=3; IntAct=EBI-6124081, EBI-1783068;
CC P48431; Q01860: POU5F1; NbExp=2; IntAct=EBI-6124081, EBI-475687;
CC P48431; P41743: PRKCI; NbExp=2; IntAct=EBI-6124081, EBI-286199;
CC P48431; P63165: SUMO1; NbExp=4; IntAct=EBI-6124081, EBI-80140;
CC P48431; Q93009: USP7; NbExp=3; IntAct=EBI-6124081, EBI-302474;
CC P48431; Q99986: VRK1; NbExp=14; IntAct=EBI-6124081, EBI-1769146;
CC -!- SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000250|UniProtKB:Q05066}.
CC Cytoplasm {ECO:0000250|UniProtKB:Q05738}. Nucleus
CC {ECO:0000250|UniProtKB:Q05738}. Note=Acetylation contributes to its
CC nuclear localization and deacetylation by HDAC3 induces a cytoplasmic
CC delocalization (By similarity). Colocalizes in the nucleus with ZNF208
CC isoform KRAB-O and tyrosine hydroxylase (TH) (By similarity).
CC Colocalizes with SOX6 in speckles. Colocalizes with CAML in the nucleus
CC (By similarity). Nuclear import is facilitated by XPO4, a protein that
CC usually acts as a nuclear export signal receptor (By similarity).
CC {ECO:0000250|UniProtKB:Q05066, ECO:0000250|UniProtKB:Q05738}.
CC -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000250|UniProtKB:P41225}.
CC -!- PTM: Sumoylation inhibits binding on DNA and negatively regulates the
CC FGF4 transactivation. {ECO:0000250}.
CC -!- DISEASE: Microphthalmia, syndromic, 3 (MCOPS3) [MIM:206900]: A disease
CC characterized by the rare association of malformations including
CC uni- or bilateral anophthalmia or microphthalmia, and esophageal
CC atresia with trachoesophageal fistula. Microphthalmia is a disorder of
CC eye formation, ranging from small size of a single eye to complete
CC bilateral absence of ocular tissues (anophthalmia). In many cases,
CC microphthalmia/anophthalmia occurs in association with syndromes that
CC include non-ocular abnormalities. {ECO:0000269|PubMed:12612584,
CC ECO:0000269|PubMed:24033328}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- BIOTECHNOLOGY: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four
CC Yamanaka factors. When combined, these factors are sufficient to
CC reprogram differentiated cells to an embryonic-like state designated
CC iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology
CC and growth properties of ES cells and express ES cell marker genes.
CC {ECO:0000269|PubMed:18035408}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA35997.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA83435.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Sox2 entry;
CC URL="https://en.wikipedia.org/wiki/Sox2";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SOX2ID44064ch3q26.html";
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DR EMBL; Z31560; CAA83435.1; ALT_INIT; mRNA.
DR EMBL; L07335; AAA35997.1; ALT_INIT; mRNA.
DR EMBL; BC013923; AAH13923.1; -; mRNA.
DR CCDS; CCDS3239.1; -.
DR RefSeq; NP_003097.1; NM_003106.3.
DR PDB; 1O4X; NMR; -; B=39-121.
DR PDB; 2LE4; NMR; -; A=39-118.
DR PDB; 6T7B; EM; 5.10 A; K=36-121.
DR PDB; 6T90; EM; 3.05 A; L=37-118.
DR PDB; 6WX7; X-ray; 2.70 A; B=39-127.
DR PDB; 6WX8; X-ray; 2.30 A; B/D=39-127.
DR PDB; 6WX9; X-ray; 2.80 A; B=39-127.
DR PDB; 6YOV; EM; 3.42 A; L=37-118.
DR PDBsum; 1O4X; -.
DR PDBsum; 2LE4; -.
DR PDBsum; 6T7B; -.
DR PDBsum; 6T90; -.
DR PDBsum; 6WX7; -.
DR PDBsum; 6WX8; -.
DR PDBsum; 6WX9; -.
DR PDBsum; 6YOV; -.
DR AlphaFoldDB; P48431; -.
DR BMRB; P48431; -.
DR SMR; P48431; -.
DR BioGRID; 112540; 705.
DR CORUM; P48431; -.
DR DIP; DIP-59913N; -.
DR IntAct; P48431; 480.
DR MINT; P48431; -.
DR STRING; 9606.ENSP00000323588; -.
DR GlyGen; P48431; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P48431; -.
DR PhosphoSitePlus; P48431; -.
DR BioMuta; SOX2; -.
DR DMDM; 1351091; -.
DR EPD; P48431; -.
DR jPOST; P48431; -.
DR MassIVE; P48431; -.
DR MaxQB; P48431; -.
DR PaxDb; P48431; -.
DR PeptideAtlas; P48431; -.
DR PRIDE; P48431; -.
DR ProteomicsDB; 55888; -.
DR Antibodypedia; 3488; 1800 antibodies from 52 providers.
DR DNASU; 6657; -.
DR Ensembl; ENST00000325404.3; ENSP00000323588.1; ENSG00000181449.4.
DR GeneID; 6657; -.
DR KEGG; hsa:6657; -.
DR MANE-Select; ENST00000325404.3; ENSP00000323588.1; NM_003106.4; NP_003097.1.
DR UCSC; uc003fkx.4; human.
DR CTD; 6657; -.
DR DisGeNET; 6657; -.
DR GeneCards; SOX2; -.
DR GeneReviews; SOX2; -.
DR HGNC; HGNC:11195; SOX2.
DR HPA; ENSG00000181449; Tissue enhanced (brain, esophagus).
DR MalaCards; SOX2; -.
DR MIM; 184429; gene.
DR MIM; 206900; phenotype.
DR neXtProt; NX_P48431; -.
DR OpenTargets; ENSG00000181449; -.
DR Orphanet; 77298; Anophthalmia/microphthalmia-esophageal atresia syndrome.
DR Orphanet; 98938; Colobomatous microphthalmia.
DR Orphanet; 35612; Nanophthalmos.
DR Orphanet; 3157; Septo-optic dysplasia spectrum.
DR PharmGKB; PA36032; -.
DR VEuPathDB; HostDB:ENSG00000181449; -.
DR eggNOG; KOG0527; Eukaryota.
DR GeneTree; ENSGT00940000160614; -.
DR HOGENOM; CLU_021123_0_0_1; -.
DR InParanoid; P48431; -.
DR OMA; QHYQGAP; -.
DR OrthoDB; 1161594at2759; -.
DR PhylomeDB; P48431; -.
DR TreeFam; TF351735; -.
DR PathwayCommons; P48431; -.
DR Reactome; R-HSA-2892245; POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation.
DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2.
DR SignaLink; P48431; -.
DR SIGNOR; P48431; -.
DR BioGRID-ORCS; 6657; 58 hits in 1094 CRISPR screens.
DR EvolutionaryTrace; P48431; -.
DR GeneWiki; SOX2; -.
DR GenomeRNAi; 6657; -.
DR Pharos; P48431; Tbio.
DR PRO; PR:P48431; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P48431; protein.
DR Bgee; ENSG00000181449; Expressed in ventricular zone and 150 other tissues.
DR ExpressionAtlas; P48431; baseline and differential.
DR Genevisible; P48431; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; TAS:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0021984; P:adenohypophysis development; IEA:Ensembl.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0006325; P:chromatin organization; NAS:UniProtKB.
DR GO; GO:0001714; P:endodermal cell fate specification; IDA:MGI.
DR GO; GO:0001654; P:eye development; IEP:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEP:UniProtKB.
DR GO; GO:0021781; P:glial cell fate commitment; NAS:UniProtKB.
DR GO; GO:0048839; P:inner ear development; IEP:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0021983; P:pituitary gland development; IEP:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:HGNC-UCL.
DR GO; GO:0070848; P:response to growth factor; IDA:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEP:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; IEA:Ensembl.
DR Gene3D; 1.10.30.10; -; 1.
DR IDEAL; IID00626; -.
DR InterPro; IPR009071; HMG_box_dom.
DR InterPro; IPR036910; HMG_box_dom_sf.
DR InterPro; IPR032643; SOX-2.
DR InterPro; IPR022097; SOX_fam.
DR PANTHER; PTHR10270:SF231; PTHR10270:SF231; 1.
DR Pfam; PF00505; HMG_box; 1.
DR Pfam; PF12336; SOXp; 1.
DR SMART; SM00398; HMG; 1.
DR SUPFAM; SSF47095; SSF47095; 1.
DR PROSITE; PS50118; HMG_BOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; Developmental protein; Disease variant;
KW DNA-binding; Isopeptide bond; Microphthalmia; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..317
FT /note="Transcription factor SOX-2"
FT /id="PRO_0000048715"
FT DNA_BIND 41..109
FT /note="HMG box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 243..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 272..280
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:P41225"
FT COMPBIAS 10..33
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..264
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 251
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT CROSSLNK 245
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VARIANT 51
FT /note="W -> R (in MCOPS3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24033328"
FT /id="VAR_075627"
FT VARIANT 74
FT /note="R -> P (in MCOPS3; unknown pathological
FT significance; dbSNP:rs104893805)"
FT /evidence="ECO:0000269|PubMed:24033328"
FT /id="VAR_075628"
FT VARIANT 79
FT /note="W -> S (in MCOPS3; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:24033328"
FT /id="VAR_075629"
FT MUTAGEN 42..43
FT /note="KR->AA: In mt1; reduced nuclear import; when
FT associated with 56-A--A-58. In mt1.2; reduced nuclear
FT import; when associated with 56-A--A-58 and 113-A--A-115."
FT /evidence="ECO:0000269|PubMed:19349578"
FT MUTAGEN 56..58
FT /note="RRK->AAA: In mt1; reduced nuclear import; when
FT associated with 56-A--A-58. In mt1.2; reduced nuclear
FT import; when associated with 42-A-A-43 and 113-A--A-115."
FT /evidence="ECO:0000269|PubMed:19349578"
FT MUTAGEN 113..115
FT /note="RRK->AAA: In mt2; reduced nuclear import. In mt1.2;
FT reduced nuclear import; when associated with 42-A-A-43 and
FT 56-A--A-58."
FT /evidence="ECO:0000269|PubMed:19349578"
FT HELIX 47..62
FT /evidence="ECO:0007829|PDB:6WX8"
FT HELIX 68..79
FT /evidence="ECO:0007829|PDB:6WX8"
FT HELIX 84..103
FT /evidence="ECO:0007829|PDB:6WX8"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:6WX8"
SQ SEQUENCE 317 AA; 34310 MW; EFCCAFE3E3A2B67B CRC64;
MYNMMETELK PPGPQQTSGG GGGNSTAAAA GGNQKNSPDR VKRPMNAFMV WSRGQRRKMA
QENPKMHNSE ISKRLGAEWK LLSETEKRPF IDEAKRLRAL HMKEHPDYKY RPRRKTKTLM
KKDKYTLPGG LLAPGGNSMA SGVGVGAGLG AGVNQRMDSY AHMNGWSNGS YSMMQDQLGY
PQHPGLNAHG AAQMQPMHRY DVSALQYNSM TSSQTYMNGS PTYSMSYSQQ GTPGMALGSM
GSVVKSEASS SPPVVTSSSH SRAPCQAGDL RDMISMYLPG AEVPEPAAPS RLHMSQHYQS
GPVPGTAING TLPLSHM
